Recent studies have demonstrated that triiodothyronine is highly localized in synaptosomal fractions of brain, as well as in peripheral adrenergic nerve terminals. A number of psychotropic drug effects are known to be effected by altering the state of thyroid function. Since thyroid hormones also independently produce marked effects on behavior, actions of iodothyronines and of psychotropic drugs may intersect at the synapse. The animal research outlined in this proposal is designed to provide information directly applicable to problems in clinical psychiatry. The immediate aims of the investigations are (1) to determine the psychobiologic implications of synaptosomally localized iodothyronines; (2) to evaluate the effects of psychotropic drugs on the function, kinetics and molecular forms of iodothyronines in nerve endings; (3) to provide and test specified psychopharmacologic agents derived from iodothyronines for their potential usefulness in the treatment of mental illness. Interactions of thyroid hormones and drugs will be studied by means of autoradiographic, immunofluorescence, neurochemical and neurobiologic procedures.